Title: Abstract 1972: Clinical impact of 6q deletion patterns in prostate cancer.
Abstract: Abstract Deletions of chromosome 6q12-22 represent the second common deletion in prostate cancer. Although most of these deletions are large and span > 50 megabases, a minimal deleted region containing 3-4 megabases was described at 6q15. MAP3K7 (at 6q15) was suggested as a potential target gene in this area. Based on the hypothesis, that large 6q deletions compromising a multitude of genes may have a different impact on the biology of prostate cancer cells than small circumscribed 6q15 deletions, a tissue microarray (TMA) containing over 7000 prostate cancers was analyzed by fluorescence in situ hybridization (FISH). All cancers were analyzed with probes for 6q12, 6q14, 6q15 (MAP3K7), 6q16, and 6q22. 3888 tumors were interpretable for all 5 probes including 463 (10.6%) showing a 6q deletion. 6q deletions were tightly linked to a negative ERG status with 15.6% deletions in ERG negative and 5.8% deletions in ERG positive cancers (p<0.0001). The frequency of 6q deletions increased with Gleason grade and pT stage. 6q deletions were found in 5.4% of ≤3+3, 10.6% of 3+4, 19.6% of 4+3, and 18.8% of ≥4+4 cancers (p<0.0001). 6q deletions occurred in 9.6% of pT2, 11.5% of pT3a, and 14.8% of pT3b carcinomas (p=0.0160). 6q deletions were also linked to early PSA recurrence (p<0.0001). Remarkably, the clinical outcome varied markedly with deletion size. PSA recurrence was more likely in cancers with 6q12-22 deletions as compared to tumors with 6q14-16 deletions (p<0.0001). Twelve genes located within 6q14-16 were functionally evaluated applying colony formation assays to prostate cell lines BPH1, DU-145, and PC-3. These analyses failed to identify a cell behavior consistent with a role as a tumor suppressor gene for MAP3K7, as well as RRAGD, ANKRD6, LYRM2, MDN1, CASP8AP2, BACH2, COQ3, MANEA, RNGTT, SLC35A1, and MMS22L. In conclusion, the strong impact of the deletion size suggests, that multiple genes on chromosome 6q12-22 might have a tumor suppressive role in prostate cancer and that alterations of more than one of these has an additive adverse effect to cells. Our data do not confirm MAP3K7 as the main target of 6q deletions in prostate cancer Citation Format: Martina Kluth, Nina Amschler, Anna Heinl, Simon Jung, Ronald Simon, Thorsten Schlomm, Guido Sauter, Sarah Jane Pauline Minner. Clinical impact of 6q deletion patterns in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1972. doi:10.1158/1538-7445.AM2013-1972
Publication Year: 2013
Publication Date: 2013-04-01
Language: en
Type: article
Indexed In: ['crossref']
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